Search: onr:"swepub:oai:DiVA.org:liu-165107" >
Neurotrophic Factor...
Neurotrophic Factors Protect the Intestinal Barrier from Rotavirus Insult in Mice
-
- Hagbom, Marie (author)
- Linköpings universitet,Avdelningen för molekylär medicin och virologi,Medicinska fakulteten
-
- Meira de Faria, Felipe (author)
- Linköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten
-
- Tinnerfelt Winberg, Martin (author)
- Linköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten
-
show more...
-
- Westerberg, Sonja (author)
- Linköpings universitet,Avdelningen för molekylär medicin och virologi,Medicinska fakulteten
-
- Nordgren, Johan (author)
- Linköpings universitet,Avdelningen för molekylär medicin och virologi,Medicinska fakulteten
-
- Sharma, Sumit (author)
- Linköpings universitet,Avdelningen för molekylär medicin och virologi,Medicinska fakulteten
-
- Keita, Åsa (author)
- Linköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten
-
- Loitto, Vesa (author)
- Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten
-
- Magnusson, Karl-Eric (author)
- Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten
-
- Svensson, Lennart (author)
- Karolinska Institutet,Linköpings universitet,Avdelningen för molekylär medicin och virologi,Medicinska fakulteten,Karolinska Inst, Sweden
-
Winberg, ME (author)
-
show less...
-
(creator_code:org_t)
- AMER SOC MICROBIOLOGY, 2020
- 2020
- English.
-
In: mBio. - : AMER SOC MICROBIOLOGY. - 2161-2129 .- 2150-7511. ; 11:1
- Related links:
-
https://liu.diva-por... (primary) (Raw object)
-
show more...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
http://kipublication...
-
show less...
Abstract
Subject headings
Close
- Increased intestinal permeability has been proposed as a mechanism of rotavirus-induced diarrhea. Studies with humans and mice have, however, shown that rotavirus leaves intestinal permeability unaffected or even reduced during diarrhea, in contrast to most bacterial infections. Gastrointestinal permeability is regulated by the vagus nerve and the enteric nervous system, which is composed of neurons and enteric glial cells (EGCs). We investigated whether the vagus nerve, serotonin (5-HT), EGCs, and neurotropic factors contribute to maintaining gut barrier homeostasis during rotavirus infection. Using subdiaphragmatic vagotomized and 5-HT3 receptor knockout mice, we found that the unaffected epithelial barrier during rotavirus infection is independent of the vagus nerve but dependent on 5-HT signaling through enteric intrinsic 5-HT3 receptors. Immunofluorescence analysis showed that rotavirus-infected enterocytes were in close contact with EGCs and enteric neurons and that the glial cell-derived neurotrophic factor (GDNF) was strongly upregulated in enterocytes of infected mice. Moreover, rotavirus and 5-HT activated EGCs (P < 0.001). Using Ussing chambers, we found that GDNF and S-nitrosoglutathione (GSNO) led to denser epithelial barriers in small intestinal resections from noninfected mice (P < 0.01) and humans (P < 0.001) and that permeability was unaffected in rotavirus-infected mice. GSNO made the epithelial barrier denser in Caco-2 cells by increasing the expression of the tight junction protein zona occludens 1 (P < 0.001), resulting in reduced passage of fluorescein isothiocyanate dextran (P < 0.05) in rotavirus-infected monolayers. This is the first report to show that neurotropic factors contribute to maintaining the gut epithelial barrier during viral insult. IMPORTANCE Human and mouse studies have shown that rotavirus infection is associated with low inflammation and unaffected intestinal barrier at the time of diarrhea, properties different from most bacterial and inflammatory diseases of the gut. We showed by in vitro, ex vivo, and in vivo experiments that neurotrophic factors and 5-HT have barrier protective properties during rotavirus insult. These observations advance our understanding of how the gut barrier is protected against rotavirus and suggest that rotavirus affects the gut barrier differently from bacteria. This is the first report to show that neurotrophic factors contribute to maintain the gut epithelial barrier during viral insult.
Subject headings
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
Keyword
- diarrhea; neurotrophic factors; permeability; rotavirus
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
-
mBio
(Search for host publication in LIBRIS)
To the university's database
- By the author/editor
-
Hagbom, Marie
-
Meira de Faria, ...
-
Tinnerfelt Winbe ...
-
Westerberg, Sonj ...
-
Nordgren, Johan
-
Sharma, Sumit
-
show more...
-
Keita, Åsa
-
Loitto, Vesa
-
Magnusson, Karl- ...
-
Svensson, Lennar ...
-
Winberg, ME
-
show less...
- About the subject
-
- NATURAL SCIENCES
-
NATURAL SCIENCES
-
and Biological Scien ...
-
and Immunology
- Articles in the publication
-
mBio
- By the university
-
Linköping University
-
Karolinska Institutet